rs199857233

Positions:

• chr10-76047241-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001305581.2(LRMDA):​c.336C>T​(p.Asn112Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000581 in 1,614,006 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (3 hom.)
• Consequence: LRMDA NM_001305581.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.62

Genes affected

LRMDA (HGNC:23405): (leucine rich melanocyte differentiation associated) This gene encodes a leucine-rich repeat protein. The encoded protein is thought to play a role in melanocyte differentiation. Mutations in this gene have been associated with autosomal recessive oculocutaneous albinism 7 (OCA7). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 10-76047241-C-T is Benign according to our data. Variant chr10-76047241-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.62 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000486 (74/152280) while in subpopulation SAS AF= 0.00311 (15/4820). AF 95% confidence interval is 0.00192. There are 0 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.336C>T	p.Asn112Asn	synonymous_variant	4/7	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.252C>T	p.Asn84Asn	synonymous_variant	3/6		NP_114413.1
LRMDA	NR_131178.2	n.690C>T		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.336C>T	p.Asn112Asn	synonymous_variant	4/7	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.252C>T	p.Asn84Asn	synonymous_variant	3/6	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.690C>T		non_coding_transcript_exon_variant	5/8	1

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 74 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000705

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000888 AC: 223 AN: 251178 Hom.: 0 AF XY: 0.00123 AC XY: 167 AN XY: 135770

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00392

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.000722

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000590 AC: 863 AN: 1461726 Hom.: 3 Cov.: 30 AF XY: 0.000774 AC XY: 563 AN XY: 727170

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00382

Gnomad4 FIN exome AF: 0.000337

Gnomad4 NFE exome AF: 0.000377

Gnomad4 OTH exome AF: 0.000695

GnomAD4 genome AF: 0.000486 AC: 74 AN: 152280 Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37 AN XY: 74450

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.000566

Gnomad4 NFE AF: 0.000706

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000426 Hom.: 0

Bravo AF: 0.000336

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000949

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 07, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.0
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs199857233; hg19: chr10-77806999;